Automated Sample Preparation for High Throughput CE-SDS-LIF of rMAbs
   Automated Sample Preparation for High Throughput CE-SDS-LIF of rMAbs
James McElroy, Oscar Salas-Solano, Lynn Gennaro, Genentech, Inc.,
South San Francisco, CA USA


CE-SDS has emerged as a powerful methodology in the biopharmaceutical industry to support analytical characterization, process development, and quality control of therapeutic monoclonal antibodies (rMAbs). Typically, UV absorbance is a common detector in CE-SDS, however, the low sensitivity (equivalent to Coomassie stained gels) has limited its application in the biotechnology industry. At Genentech Inc., we demonstrated that precolumn labeling of rMAbs with 5-TAMRA.SE and LIF detection can be used for CE-SDS analyses as a replacement for silver-stained SDS-PAGE to quantify low-level impurities and rMAb size variants and to determine lot-to-lot consistency. This method requires the use of manual dye-labeling protocols. The protein sample must be buffer-exchanged to provide the optimal conditions for fluorescence dye labeling followed by excess dye removal purification. This sample preparation procedure can often be the bottleneck in sample throughput, and automated procedu res are desirable. This poster describes an automated sample preparation protocol for CE-SDS-LIF using a liquid handling robot. This system allows the automation of the dye labeling protocol as well as decreasing the amount of protein sample required by ten fold. This greatly increases throughput while reducing analyst sample handling and quantity of sample used.